可降解与不可降解涂层雷帕霉素洗脱支架植入后高敏C反应蛋白和白细胞介素6水平变化

目的 观察可降解涂层与不可降解涂层雷帕霉素药物洗脱支架植入后循环与局部高敏C反应蛋白和白细胞介素6水平变化.方法 连续入选118例接受PCI治疗植入1枚支架的不稳定型心绞痛患者,分为不可降解涂层组(n=65)和可降解涂层组(n=53).于术前、术后即刻、48 h、7天及9月时抽取静脉血,术前、术后即刻及术后9月冠状动脉造影随访时以微导管抽取冠状动脉局部血液,测定高敏C反应蛋白和白细胞介素6水平.结果 两组基本临床资料、PCI术情况无明显差异.两组术后即刻支架局部血清白细胞介素6水平较术前显著升高;术后48 h和7天循环高敏C反应蛋白和白细胞介素6水平明显高于术前.两组间比较,PCI术前、术后即刻、48 h、7天和9月时循环及局部高敏C反应蛋白和白细胞介素6水平均无明显差异.结论 可降解涂层与不可降解涂层雷帕霉素洗脱支架对术后循环与局部炎症反应的影响可能相似.     

黄芩苷调节高脂饲养大鼠肝脏脂质代谢及其机制

近年来,非酒精性脂肪性肝病(NAFLD)发病率有逐年上升的趋势,但目前对NAFLD尚无有效的疗法,减少肝脏细胞内脂质含量有望减轻高脂饮食对肝脏的危害.有研究结果表明,黄芩苷对肝脏具有较好的保护作用,但其机制不明.腺苷酸活化蛋白激酶(AMPK)是脂质调节的关键靶蛋白,参与脂肪酸、甘油三酯(TG)及胆固醇的调节.本研究主要探讨黄芩苷对高脂喂养大鼠肝脏脂质代谢的影响及AMPK信号通路是否参与该调控.     

2009年广东省甲型流行性感冒暴发流行期间首株甲型H1N1流行性感冒病毒血凝素基因分析

目的 检测和分析2009年广东省甲型流行性感冒(流感)暴发流行期间首株甲型H1N1流感病毒血凝素(HA)基因.方法 对2009年广东省首例确诊的甲型H1N1流感患者的咽拭子进行病毒分离,取细胞培养上清液提取病毒核酸,采用HA基因的特异性引物进行RT-PCR,PCR产物进行克隆、测序和同源性分析.结果 获得2009年广东省首株甲型H1N1流感病毒的HA基因,大小为1710 bp,命名为A/GuangzhouSB/01/2009(H1N1)HA,GenBank登录号为GQ268003.与疫情发源地近期报告的277株甲型H1N1流感病毒的HA基因比对,同源性为99.0%～99.8%;其中与美国报告的病毒株的同源性高达99.8%,与患者发病前曾到美国旅游的流行病学史一致.与25株中国季节性甲型H1N1流感病毒的HA基因比对,同源性为72.3%～85.6%.结论 2009年广东省甲型流感暴发流行期间首株甲型H1N1流感病毒与目前流行的甲型H1N1流感病毒同源性高,与中国季节性甲型H1N1流感病毒同源性较低.     

磷脂酰肌醇3-激酶/蛋白激酶B信号通路对CD40介导胃癌细胞侵袭与转移的研究

目的 探讨可溶性CD40配体(sCD40L)联合磷脂酰肌醇3-激酶/蛋白激酶B(P13K/Akt)信号通路特异性阻断剂LY294002对胃癌AGS细胞体外增殖及侵袭、转移的影响;初步探讨其可能的作用机制.方法 将细胞分成对照组(仅加入含10%胎牛血清的RPMI 1640培养液)、LY294002组(20μmol/L)、sCD40L组(2μg/ml)和LY294002+sCD40L组.四甲基偶氮唑盐法检测不同浓度sCD401,及联合LY294002对细胞增殖的影响;Transwell实验和划痕实验分析细胞侵袭、转移能力的改变;Western印迹检测细胞P13K、p-Akt、血管内皮生长因子(VEGF)蛋白表达的变化.结果 LY294002作用后细胞生存率为65.7%,sCD40L作用后为70.1%,LY294002+sCD40L组生存率为41.3 0A,差异有统计学意义(P<0.05).LY294002+sCD40L组细胞的划痕愈合速度较sCD40L和LY294002组明显减慢.LY294002+sCD40L组平均每个视野的细胞数较sCD40L和LY294002组明显减少.与对照组相比,sCD40L使P13K、p-Akt、VEGF蛋白表达升高,与LY294002联合作用后,P13K,p-Akt、VEGF蛋白表达明显降低.结论 阻断P13K/Akt信号途径可显著增强sCD40L对人胃癌AGS细胞增殖及侵袭、转移的抑制作用,为胃癌的生物治疗提供一种新的方法.     

吲哚美辛对慢性阻塞性肺疾病大鼠肿瘤坏死因子α和骨骼肌蛋白质分解代谢的影响

目的 观察吲哚美辛对慢性阻塞性肺疾病(COPD)大鼠TNFα和骨骼肌蛋白质分解代谢的影响.方法 大鼠分为COPD模型组和健康对照组.COPD模型组制作COPD大鼠模型.造模成功后,以低于健康对照组平均体重90%为标准将大鼠分为COPD营养不良组和COPD营养正常组.COPD营养不良组按随机区组分为:COPD营养不良非干预组(A组),COPD营养不良吲哚美辛低剂量干预组(B组),COPD营养不良吲哚美辛中剂量干预组(C组),COPD营养不良吲哚美辛高剂量干预组(D组).检测各组吲哚美辛干预前后体重、血清TNFα及膈肌、伸趾长肌匀浆中3-甲基组氨酸和酪氨酸含量.结果 (1)吲哚美辛干预前,COPD营养不良组大鼠血清TNFα水平均明显高于COPD营养正常组、健康对照组;吲哚美辛干预后,B组、C组、D组大鼠血清中TNFα含量比A组显著降低,尤以C组最明显.(2)吲哚美辛干预后,大鼠膈肌、伸趾长肌匀浆中3-甲基组氨酸和酪氨酸含量上升,体重回升,尤以C组最明显.(3)COPD模型组大鼠血清TNFα含量与体重、膈肌、伸趾长肌重量呈负相关(r分别为-0.846、-0.778、-0.772,P＜0.01).结论 TNFα参与了COPD营养不良、骨骼肌萎缩的发生,吲哚美辛可降低COPD营养不良大鼠血清中TNFα水平及骨骼肌蛋白分解代谢,从而部分改善COPD营养不良大鼠的骨骼肌萎缩.     

PAMPA permeability, plasma protein binding, blood partition, pharmacokinetics and metabolism of formononetin, a methoxylated isoflavone

Formononetin (FMN) is a methoxylated isoflavone which is the major constituent in red clover and in commercially available extracts of this plant. In this study, we investigated the parallel artificial membrane permeability assay (PAMPA) permeability, protein binding, blood uptake characteristics, pharmacokinetics and metabolism of FMN. The permeability study samples were analyzed by HPLC-PDA method; whereas the pharmacokinetic study, protein binding and whole blood partitioning samples were analyzed by LC-MS/MS method. The PAMPA permeability of FMN was found to be high at pH 4.0 and 7.0. Plasma protein binding of FMN was found to be 93.61 ± 0.44% and 96.14 ± 0.15% at the tested concentration of 50 and 150 ng/mL, respectively. FMN reached equilibrium fast between red blood cells (RBCs) and plasma, and the partition coefficients between RBCs and plasma (K_RBC/PL) were independent of the initial rat blood concentrations of FMN. The bioavailability of unchanged/free FMN was found to be poor, i.e. approximately 3%. FMN was found to have a high clearance (5.13 L/h/kg) and a large apparent volume of distribution (14.16 L/kg). Circulating conjugates (glucuronides/sulfates) of FMN and daidzein (DZN) were quantified using enzymatic hydrolysis of plasma samples. The levels of isoflavone glucuronides/sulfates were found to be much greater than that of the corresponding aglycones.     

The use of a novel tobacco treatment process to reduce toxicant yields in cigarette smoke

The US Institute of Medicine has encouraged the pursuit and development of potential reduced-exposure products (PREPs) - tobacco products that substantially reduce exposure to one or more tobacco toxicants and can reasonably be expected to reduce the risk of one or more specific diseases or other adverse health effects. One potential approach is to reduce levels of some smoke toxicant precursors, such as proteins and polyphenols, in tobacco. We describe a treatment process involving aqueous tobacco extraction and treatment with protease; filtration of the extract to remove peptides, amino acids and polyphenols, and recombination of extract and treated tobacco. The process reduced levels of protein nitrogen (59%), polyphenols (33-78%) and nicotine (12%) while sugars increased 16%. ISO mainstream smoke yields of 43 toxicants were measured from cigarettes containing treated tobaccos; lower yields of tar, nicotine, carbon monoxide (16-20%), acrylonitrile, ammonia, aromatic amines, pyridine, quinolene and hydrogen cyanide (33-51%), tobacco specific nitrosamines (25-32%); phenolics (24-56%), benzene (16%), toluene (25%) and cadmium (34%) were obtained. There were significantly increased yields of formaldehyde (49%) and isoprene (17%). Reductions in sidestream yields of nitrogenous smoke toxicants and increases in sidestream yields of several carbonyls, benzo(a)pyrene and isoprene were also observed.     

Synthesis and biological activities of 2-amino-thiazole-5-carboxylic acid phenylamide derivatives

In an attempt to develop potent and selective anti‐tumor drugs, a series of novel 2‐amino‐thiazole‐5‐carboxylic acid phenylamide derivatives were designed based on the structure of dasatinib. All compounds were synthesized by a systematic combinatorial chemical approach. Biological evaluation revealed that N‐(2‐chloro‐6‐methylphenyl)‐2‐(2‐(4‐methylpiperazin‐1‐yl)acetamido)thiazole‐5‐carboxamide ( 6d ) exhibited high antiproliferative potency on human K563 leukemia cells comparable to dasatinib. Against mammary and colon carcinoma cells 6d was either inactive (MDA‐MB 231) or distinctly less active (MCF‐7 and HT‐29: IC₅₀ = 20.2 and 21.6 µM, respectively). Dasatinib showed at each cell line IC₅₀ < 1 µM. The results of this structure activity relationship study clearly documented that the pyrimidin‐4‐ylamino core of dasatinib is responsible for the anti‐tumor activity against non‐leukemia cell lines.     

分子排阻色谱法测定水解蛋白注射液中高分子物质

目的:采用分子排阻色谱法测定水解蛋白注射液中小分子肽的分子量。方法:采用TSK-GEL G2000SWXL色谱柱(7.8mm×300 mm,5μm),以磷酸盐缓冲液(pH 6.8)(含0.1 mol.L-1Na2SO4与0.05%NaN3)为流动相,流速1.0 mL·min-1,柱温30℃,检测波长280 nm。结果:水解蛋白注射液中分子量大于胰岛素的高分子物质含量均在5%以下。结论:该方法简单,重现性好,可以作为控制水解蛋白注射液中高分子物质的方法。     

胎盘蛋白13和glycodelin在子痫前期患者血清中的表达

目的  探讨胎盘蛋白13（PP13）和妊娠相关子宫内膜蛋白（glycodelin）在子痫前期患者血清中的表达。方法  采用酶联免疫吸附试验（ELISA）分别测定子痫前期组（包括轻度子痫前期和重度子痫前期组）及正常妊娠妇女外周血血清中PP13、glycodelin的浓度。结果  ①子痫前期组孕妇血清PP13的水平显著高于正常妊娠组（P＜0.01）,而glycodelin的水平显著低于正常妊娠组（P＜0.01）;②轻度子痫前期组PP13水平低于重度子痫前期组（P＜0.01）,而轻度子痫前期与重度子痫前期组的glycodelin水平无明显差异（P＞0.05）;③PP13、glycodelin在子痫前期患者中不具有相关性;④血清PP13的水平与孕周相关。结论  子痫前期患者血清中PP13、glycodelin水平均异常表达,可能参与了子痫前期的发生,发展。同时血清PP13水平与病情的严重程度有关,可能是预测疾病进展的一项指标。